Protective effects of andrographolide on septic mice and the related mechanism

Abstract

Objective To investigate the protective effects of andrographolide on septic mice and to explore the underlying mechanism.Methods Sepsis model was induced by cecal ligation and puncture(CLP)in mice.A total of 64C57BL/6mice were evenly randomized into 4 groups:a sham group,a CLP group,a dimethyl sulfoxide (DMSO)group and an andrographolide(AND)group.The mice were injected intraperitoneally with 0.2mL normal saline,0.2mL 5% DMSO or 0.2mL andrographolide(10mg/kg)at 1h,6hand 12hafter surgery.The survival rates were assessed 7days after surgery and the survival curve was plotted.Another 48C57BL/6mice were grouped as above.The peripheral blood,peritoneal lavage fluid(PLF),lung and liver tissues were harvested 24hafter operation.Polymorphonuclear leukocyte(PMN)count in PLF was determined.Bacterial loads in the peripheral blood sample and PLF were also determined.The levels of TNF-α,IL-6and IL -10in the blood samples were detected by ELISA.The lung and liver tissues were observed and analyzed by hematoxylin- eosin staining.Results Compared with CLP group,AND group had a significantly increased survival rate 7days after operation (P0.01),a significantly decreased PMN count in PLF (P0.01),a significantly enhanced bacterial clearance capability in both blood and PLF(P0.01),significantly decreased serum TNF-αand IL-6levels,significantly increased IL-10level, and significantly alleviated lung and liver tissue injuries (P0.01).The above parameters were not significantly different between the DMSO group and CLP group.Conclusion Andrographolide has protective effect against CLP-induced sepsis in mice,which might be associated with regulation of the immunological function,enhancement of bacterial clearance and inhibition of excessive inflammatory response during sepsis.